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INTERSTITIAL LUNG DISEASE |
and ß in steroid sensitive and steroid insensitive interstitial lung diseases
1 Institut dInvestigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
2 Servei de Pneumologia i Al.lèrgia Respiratòria, Institut Clínic de Pneumologia i Cirurgia Toràcica, Hospital Clínic, Departament de Medicina, Universitat de Barcelona, Barcelona, Spain
3 Servei dAnatomia Patològica, Hospital Clínic, Barcelona, Spain
4 Servei dOtorinolaringologia, Hospital Clínic, Barcelona, Spain
5 Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
Correspondence to:
Correspondence to:
Dr C Picado
Servei de Pneumologia, ICPCT, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain; cpicado{at}ub.edu
Background: Sensitivity to glucocorticoids may be related to the concentration of glucocorticoid receptors
(GR
) and ß (GRß). A study was undertaken to assess GR
and GRß expression in steroid insensitive interstitial lung disease (idiopathic pulmonary fibrosis (IPF)) and steroid sensitive interstitial lung diseases (sarcoidosis and cryptogenic organising pneumonia (COP)).
Methods: Lung tissue was obtained from control subjects and from patients with IPF, sarcoidosis, and COP. Pulmonary function tests were carried out at the time of lung biopsy and every 3 months. GR
and GRß expression was evaluated by both competitive RT-PCR and immunohistochemistry. Data are presented as median and 2575th percentile.
Results: GR
mRNA expression (105 cDNA copies/µg total RNA) was higher in patients with steroid sensitive interstitial lung diseases (10.0; 7.814.9; n = 11) than in patients with IPF (4.4; 3.26.6; n = 19; p<0.001). GRß expression was at least 1000 times lower than that of GR
and did not differ between the three groups. A negative correlation was found between GR
mRNA levels and the fibrotic pathology score of the tissue (r = 0.484, p<0.01) and a positive correlation was found between GR
mRNA levels and improvement in forced vital capacity (r = 0.633; p<0.01) after treatment of patients with glucocorticoids. Immunoreactivity for GR protein was also higher in patients with sarcoidosis and COP than in those with IPF.
Conclusion: The variable response of some interstitial lung diseases to steroid treatment may be the result of differences in the expression of GR
.
Abbreviations: COP, cryptogenic organising pneumonia; IPF, idiopathic pulmonary fibrosis; GR, glucocorticoid receptor; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; TLCO, carbon monoxide transfer factor
Keywords: glucocorticoids; glucocorticoid receptors; idiopathic pulmonary fibrosis; sarcoidosis; cryptogenic organising pneumonia
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